dibutyryl-cyclic-gmp and dibutyryl-cyclic-3--5--cytidine-monophosphate

cAMP-dependent protein kinase (PKA) and phospholipid-dependent protein kinase (PKC) play a role in nerve growth factor (NGF)-mediated differentiation. In PC12 cells, NGF causes neurite outgrowth and increases the number of voltage-gated Na+ channels. Neurite outgrowth involves in part activation of PKC. How NGF regulates Na+ channel number is unknown. Using patch-clamp techniques, we find that agents activating PKC, including phorbol esters and a ras oncogene product (p21) that induces neurites, caused little increase in channel number. In contrast, agents increasing intracellular cAMP were as effective as NGF. A specific protein inhibitor of the PKA catalytic subunit blocked increases by NGF or cAMP. Thus, NGF increases Na+ channel number in PC12 cells in part by activating PKA but apparently not PKC.

Topics: 1-Methyl-3-isobutylxanthine; Adrenal Gland Neoplasms; Animals; Bucladesine; Cell Differentiation; Cell Line; Colforsin; Cyclic CMP; Dibutyryl Cyclic GMP; Dimethyl Sulfoxide; Electric Conductivity; Electrophysiology; Gene Expression; Genes, ras; Kinetics; Nerve Growth Factors; Pheochromocytoma; Protein Kinases; Rats; Sodium Channels; Tetrodotoxin